AMPLIFICATION AND DIFFERENTIAL EXPRESSION OF MEMBERS OF THE ERBB-GENEFAMILY IN HUMAN GLIOBLASTOMA

The objective of the present study was to determine the frequency of a mplifications of three different members of the erbB gene family in hu man glioblastoma multiforme (GEM). We investigated 47 glial tumors (37 GEM WHO grade IV, 5 anaplastic astrocytomas WHO III and 5 astrocytoma s WHO II) by Southern and Western analysis, and immunocytochemistry. G ene amplification of erbB genes in human malignant gliomas was restric ted to the EGF receptor (EGFR) gene, erbB-1. We found amplification of the EGFR gene in 49% (18/37) of GEM but not in the astrocytomas WHO I I/III. The erbB-2 and erbB-3 genes showed no amplification in the tumo r specimens investigated in this study. At the protein level we found overexpression of the EGF receptor in 86% (32/37) by Western analysis and in 92% (34/37) by immunocytochemistry. Expression of the ERBB2 pro tein was present in 54% (20/37) but immunoreactivity was much weaker t han for EGF receptor and in most cases barely detectable by Western an alysis and immunocytochemistry. The ERBB3 protein was not expressed in the glial tumors investigated in this study. Of the three erbB genes only gene amplification and overexpression of the EGF receptor seems t o have an impact on tumor progression of human gliomas. Our data from immunohistochemistry indicate that ERBB2 expression in GEM is closely correlated with EGF receptor levels and is therefore not useful as an independent prognostic parameter.